The effectiveness of the ensemble perturbation method, in which many pairs of perturbed and unperturbed molecular dynamics simulations are executed for the ensemble average, has been demonstrated by calculating the subtle anisotropic structural change of carbonmonoxy myoglobin (MbCO) triggered by ligand photolysis. The results show that Mb largely expands in the direction perpendicular to the heme plane and slightly contracts in the horizontal one. This agrees well with the report in the transient grating experiment. In addition, it is suggested that the expansion contributes strongly to the fast energy-transfer process to the water solvent because it is undergone almost within several picoseconds. The mechanical work done on the solvent by the expansion within 1 ps was thermodynamically estimated to be 4.8 kcal/mol.